Let me tell you the hard part about writing about epigenetics: most of your audience has no idea what you’re talking about, but is pretty sure that they can use it, whatever it is, to justify every bit of folk wisdom/nonsensical assumption that they have. So while you’re explaining how it’s a very real and important biological process that is essential for development and learning and behavior, half your readers are using the biology to confirm their biases about evolution and inheritance, and the other half already know all the basic stuff and want to get to the Evisceration of the Wrong, which is always the fun part anyway.
So I’ve split this post in two: there’s a section on the basics of what epigenetics is, and there’s a section on what epigenetics is not, and why. Read whatever part floats your boat.
Part I: The didactic bit for those who don’t know what epigenetics is
Epigenetic inheritance is a simple enough concept, but man oh man the baggage that gets loaded onto it…in many ways, the assumptions people make about it are more interesting than the phenomenon itself. Epigenetics is always in the news lately, but rather than just digging into the details of the paper that prompted all the media coverage, I want to step way back to the beginning and try to defuse a few misconceptions, and also say a few things about popular wrong ideas, and why they might be popular.
Epigenetics refers to mechanisms that modify the expression of a genetic signal. It’s a separate set of signals from the sequence of nucleotides in the genome; for instance, you might have a gene for an enzyme, in which the sequence of amino acids in the protein is specified by a chain nucleotides, but the cell also has ways to modify that chain that don’t change the sequence, but do affect whether the enzyme gets made or not. One method is to add a methyl group — a single carbon and 3 hydrogens — to the sugar backbone of the DNA for the gene. That leaves the sequence intact, but acts as a signal to the RNA synthetic machinery to ignore that piece of DNA. Methylation is one mechanism of transcriptional silencing.
There are many other mechanisms of epigenetic modification than methylation: there are DNA associated proteins, like the histones, that can be chemically modified to affect gene activity, and some of these can activate instead of silencing genes. There are transcription factors that can control gene activity by their presence or absence. It gets extremely complicated when trying to track all the components that modulate a gene’s pattern of expression.
Furthermore, epigenetic modifications are passed on from generation to generation. When a cell divides and replicates its DNA, it also dutifully copies the same pattern of methylation from the old DNA strand to the new strand. This is important in maintaining a hierarchical pattern of cell types: when one of your liver cells divides, the new daughter cell does not have to go through a complicated series of differentiation steps or in any way struggle to set what kind of cell type it is. It inherits all the epigenetic marks of its parent cell, all the methylation, all the histone modifications, all the transcription factors, that specify that it is also a liver cell.
For all you coders out there, it’s like object-oriented programming. When you create a new instance, all the code (the DNA) is the same, but we also have an initiation routine that duplicates all the local variables. (That probably doesn’t help at all if you don’t program, but I hope it makes sense to all the computer nerds reading about biology.)
Does epigenetic inheritance have evolutionary implications? Yes, it does. It represents a kind of memory that is passed down for one or a few generations. Imagine a protist that has switched on a set of genes that help it adapt to a particular environment. It would be advantageous for all of its daughter cells, which are existing in that same environment, to carry that appropriate pattern of gene expression right from the beginning — to be preloaded with properties that immediately adapt them.
Epigenetics also confers greater plasticity on individuals. An organism could, for instance, be able to thrive in both cool and warm temperatures by switching appropriate genes on and off. In this case, though, the specific state of those genes doesn’t have to be transmitted from parent to offspring — it’s a kind of inherited flexibility.
But otherwise, it’s hard to see a specific evolutionary effect. The whole point of epigenetic modification of gene expression is that it is responsive to the environment! The state of gene expression can be rewritten during any generation by a new set of conditions.
Another problem is that most of the popular interest in epigenetic inheritance focuses on multicellular organisms. The only cells that matter in this case are germ line cells — that is, guys, only physiological effects that modify cells in your testes can be passed on, and ladies, it’s only your ovaries that count. These are highly specialized cells, with a great many epigenetic modifications specific to their functions as gametes. Their most important role is to be prepped to be totipotent, to be primed to follow a broad developmental pathway, and the epigenetic state of many genes will be overwritten to condition them to do that job. If a person has gene X methylated in their tissues, and their child is found to have gene X methylated as well, it’s not necessarily a case of epigenetic inheritance — that gene might have been demethylated in the gamete, and the methylated state in the adult is a consequence of modification during their life history.
So it’s kind of weird to see studies of epigenetic states in one generation of adults, comparing them to the epigenetic states in a different generation of adults. Those individuals went through a single-celled bottleneck, where the epigenetic marks on many genes were explicitly reset to a specific condition appropriate for gametogenesis and embryogenesis, and not to, for instance, a state appropriate to the neurons relevant to a behavior. The genes that have a variable pattern of epigenetic marks at this point may be irrelevant to the essential activities that are going to occur during development, and what these researchers studying epigenetic inheritance are actually looking at may, in many cases, be pure noise.
Part II: the bit about silly misconceptions
I’ve been gathering stories about epigenetics from science and pop culture for a while now. It’s a painful exercise in witnessing science harnessed to support magical thinking — it seems a lot of people want a natural, material explanation to justify their belief that behavior now will modify their biological legacy in a significant way, so they are happy to embrace nonsensical interpretations.
So, for instance, epigenetics is apparently an explanation for racial memory.
May our DNA Carrying also spiritual and cosmic memories passed down in genes from our ancestors?
Sounds ridiculous, I know, but the commenters at that link are lapping it up.
I have written about this for a long time. I did believe in reincarnation, but the more I looked into it the more it was obvious that it was genetic memory. Good to see that I was right.
Great! We’re going to replace reincarnation pseudoscience with genetic memory pseudoscience.
Even once you dismiss the bogus kookery, though, there are still real concerns. One is that there is a bizarre trend towards blaming cultural, sociological, and psychological problems on biology, like this claim that trauma may be woven into DNA of native Americans.
Folks in Indian country wonder what took science so long to catch up with traditional Native knowledge. “Native healers, medicine people and elders have always known this and it is common knowledge in Native oral traditions,” according to LeManuel “Lee” Bitsoi, Navajo, PhD Research Associate in Genetics at Harvard University during his presentation at the Gateway to Discovery conference in 2013.
According to Bitsoi, epigenetics is beginning to uncover scientific proof that intergenerational trauma is real. Historical trauma, therefore, can be seen as a contributing cause in the development of illnesses such as PTSD, depression and type 2 diabetes.
No. Just no. The oppression of American Indian populations is terrible and real, but some kind of poorly understood claim of warping of their DNA is a damaging distraction. The problem is poverty, exploitation, and neglect, which has more direct and immediate effects on the well-being of people. Indians are not suffering because of genetic damage, but because our society values their lives less and traps them in difficult and unsupportive environments.
I don’t think that article intends it that way, but this is a variant of the old canard that alcoholism in Indian populations can be blamed on their genetic inferiority at metabolizing alcohol, rather than on despair and deprivation. They do have differences in the frequency of many alleles from European populations, but the disreputable interpretation that those variations represent differences in quality is simply not true. Alcoholism is a complex problem that cannot be reduced to a single enzyme.
In fact, there’s no evidence that Native Americans are more biologically susceptible to substance use disorders than any other group, says Joseph Gone, associate professor of psychology at the University of Michigan. American Indians don’t metabolize or react to alcohol differently than whites do, and they don’t have higher prevalence of any known risk genes.
It’s all just naive reductionism, and it’s really annoying. It’s also being applied trivially to all kinds of behaviors.
Why can’t your friend “just get over” her upbringing by an angry, distant mother? Why can’t she “just snap out of it”? The reason may well be due to methyl groups that were added in childhood to genes in her brain, thereby handcuffing her mood to feelings of fear and despair.
Aaaargh. Really? We’re going to go there? One of my earliest memories is of my mother showing me how to use a toy microscope. Obviously, this removed methyl groups from the genes responsible for enjoying lenses and light, while selectively adding a -CH3 to those genes that might have misdirected me towards astronomy. I don’t actually have any evidence for that, but hey, it makes sense, right, and you can’t argue with chemistry!
Yes, gene expression is constantly being tweaked and modified throughout your life, different cell types have different epigenetic marks, and experiences do change the pattern of activity and molecular behavior of your neurons. Changes in the way you think don’t occur without changes in the physical properties of your brain. But it is comically absurd to think you can explain a complex, higher-level psychological phenomenon like resentment of your mother to a facile comment about one kind of chemical reaction.
Epigenetics has become the new “gene for X” of the 21st century. I recall (usually with a barely suppressed glower and curl of the lip) all the sensationalism of researchers looking for the “gay gene” way back when I was in grad school. Even then, it made no sense: I’d been working on flies and fish, and the lessons we were getting over and over is that behavior is an extremely complex emergent property of interactions between multiple genes and their environment, and yet we’ve got people thinking they can find single genes that are responsible for phenomena as complex and diverse as human sexual attraction? I cringed when I saw the t-shirts thanking Xq28 for their gayness. That one’s sexual preferences were not consciously chosen is not synonymous with simple allelic inheritance directly generating them — your brain is shaped by genes, development, hormones, and experience.
So no “gay gene” has been found. So instead, I think in frustration that their jejune genetic determinism is unsatisfied by correlated patterns of nucleotides, some researchers have turned to searching for epigenetic causation. There are no gay genes. There are also no gay epigenetic marks. That is not to say that there are no differences in how gays vs. straights view sexual behavior, but that you can’t simply say that it’s due to histone differences or carbons tagged onto a sugar backbone. It’s like trying to explain a car accident with “It’s like F=ma, dude. I didn’t hit your car, blame that douche, Newton.”
Also, every time we look at the studies behind these claims, they always seem to have tiny sample sizes and statistically minuscule effects.
Fortunately, xkcd provided a neat summary to wrap these two parts up.
The short answer: whenever someone tells you that they have a simple explanation for how biology works, especially when they reduce it all to chemistry or code, you can tell them they’re full of shit.
Showing them the google source code is too easy, though. I like to point them at Online Mendelian Inheritance in Man, and tell them to search for anything — gene, behavior, disorder, whatever. Then try and follow the links to the literature, which will be overwhelming enough, and then track any gene found to the actual sequence and genomic information. Come back and talk to me once you’ve figured it all out.
Was this inspired by the latest Minute Earth video?
https://youtu.be/AvB0q3mg4sQ
Well, I wasn’t expecting it to post the video…
My daughter is an undergrad studying biology, and the tiny little reflected view I get of what’s going on in that world is, if you don’t mind the language, fucking awesome. The level of understanding that even mostly well-educated people have of biology is basically zero. At best. It’s usually so far from reality that it is, to (probably) quote Wolfgang Pauli, not even wrong. So no wonder people use whatever buzz words (like ‘epigenetics’) they can latch onto to provide evidence for whatever pet bullshit theory they’re trying to sell.
I hadn’t seen that video, but I have serious reservations about the study as explained in the video. They really expect that there is A GENE responsible for responses to a specific odorant (well, maybe if it’s a receptor), and that it’s regulatory state is set in the testes by olfactory stimuli, and that that state is unaffected by gametogenesis, and that it is expressed in the appropriate areas of the baby rat sensory tissue? I don’t know, man. I’d have to read the paper, but there’s a whole series of steps that would have to be demonstrated to my satisfaction before I’d believe it.
There’s a kind of bell curve for the relationship between how much you know about something and how simple you think the subject is. First, you think it’s very difficult, then you think it’s very easy, and then you realize that it’s way more complex than you ever thought. It’s only at the last step that you’re in a position to contribute to the area.
Williamgeorge @ 1:
The first sentence says rats aren’t known for running away from the sweet scent of fruit. I have rats, and a majority of them do just that – in particular, the scent of bananas and strawberries make them run for cover, and they won’t have anything to do with the fruit, but they will happily eat something like banana chips. I don’t know biology at all, but statements like that are seriously suspect.
I was a microchip designer and then in IT for many years when I started looking at genetics from a programming point of view. I came across epigenetics and discussed it with my father (a zoologist head of dept by trade) and we had some interesting arguments but the power of epigenetics (to me) is quite amazing.
If a seed can be pre-programmed by the parent to turn on the genes required to grow in the local conditions then it has an evolutionary advantage over its bretheren that have the same genes but are wasting energy expressing others that are unsuitable to the local environment. Once this trick has evolved it gives huge advantages. My own experiments with growing seed taken from plants growing on a plot of land and comparing them with genetically identical seeds from other soils seem to show massive improvements (>30%) in yields for locally sourced seed – the seedlings get away so much faster as they can exploit the soil rather than experiment with genes to see which work.
I think we will find it is fundamental to a lot of life forms.
In the case of the descendants of Norwegian famine survivors, I’d like to know how they distinguished epigenetic causes from, say, family traditions of frugality leading to a different diet.
Original article: http://www.nature.com/neuro/journal/v17/n1/full/nn.3594.html It’s in Nature Neuroscience, so they did a lot of experiments… although maybe not all the most useful ones.
To be fair, they indeed looked at “a known odorant receptor (Olfr151)”
Closest I was able to find from a cursory look at the article:
but
…although they go on to suggest that
I remain skeptical, but it’s not *quite* as simple as the video may have made it seem ;)
Thank you so much for this quick lesson, I really learned a lot. Now I do recall seeing experiments indicating that mice can pass on epigenetic changes, though I don’t recall any specifics. You mention the single cell bottleneck which would limit this effect, but is this just bunk or something we’ve only started to understand? I can definitively see the benefit in “priming” the offspring for the environment they’re brought into, and considering how “clever” nature is I wouldn’t be surprised if we found highly developed mechanisms for this.
The pop-epigenetics trope that really annoys me is the one where a study shows some kind of marginal maternal effect one or two generations out, which is interpreted to maybe be caused by epigenetic inheritance. Which is then taken to mean that “ZOMFG Darwin was wrong and biology is a lie and my own nebulous armchair folk-lamarckism is cutting edge science that has been proven true forever!!!” Mostly this comes from internet contrarians, but more restrained versions do come out of university press releases and sort of legit science journalism.
I just watched the BBC/PBS/Nova “The ghost in your genes” documentary and they talked about traumatic events being passed down from one generation to the next in rats and humans. I have not read the studies that these are based on, but there may be something to it. Here’s a website that gives a good summary of “The ghost in your genes” for anyone interested.
Epigenetics is the new quantum.
From the summary I posted @12 about the Swedish town.
To say that there is a causation with this correlation, strikes me as anomaly hunting. Personally I would just say that it is preliminary evidence, but more research needs to be done to elucidate the connections.
Igneous Rick@13
Besides being the new quantum, Did you know that “The science of epigentics therefor is showing strong parallels to Hahnemann’s theory of miasms.”
Igneous Rick #13, when does Deepak Chopra come on stage?
“Your life is an epigenetic reflection of the universe’s mind. Embrace the ancestors of your inherent disorders.”
madtom1999 #7:
I hate to break it to you, but that is not epigenetics. That is plain-vanilla genetics and natural selection.
parasiteboy #14:
ISTM, that if the response to reduced food supply in one generation is to increase the mortality of the grandchildren, that would be kinda against the principle of natural selection, wouldn’t it? In other words, if my neighbor and I suffered through a famine, and he had some sort of mechanism that increased the chance of his grandchildren dying 40 years later and I didn’t, I would expect to have many more descendants in the future than he would, wouldn’t I?
PZ,
Just MHO, but I’m not sure that Object Oriented code simile/analogy works.
I think you are saying that the method code of an object is like the DNA, the same for all objects of a class, and the object’s data members can act like epigenetic information and adjust the behavior of the code without modifying the code itself.
The code/DNA analogy is a slippery one, as you are well aware, so I’m nervous about using it here. And data members do more than just tweak the code’s behavior, or at least, that’s a very unusual way to thing about what data members do (again, IMHO).
But there are two basic types of constructors for making objects. Default constructors (which provide the same initial data member state for all created objects) and copy constructors, which copy the data member state from another object. (There are also parameterized constructors, but this is already getting too complicated). For the liver cell example, I think you mean specifically copy constructor, since the parent cell is the source for the epigenetic information (data member content) for the daughter cells.
In summary, I think this gets technical enough, quickly enough, that I’m not sure it helps clarify the process. Again, just one impression from one person.
Thanks for listening.
Over 50 years after the woo made its first appearance, when some of the most influential theorists were peddling it. Roughly speaking — I couldn’t give you many reliable dates about Chopra’s career.
But I don’t know, maybe it doesn’t make a very good analogy with epigenetics. Was epigenetics sold like this originally by some of its inventors, and now people are trying to forget/ignore/revise the history which led to where we are now, by blaming our troubles on a handful of crank outsiders who aren’t much of an influence on Serious Scientists™? Because honestly, as sad as it is, it would still be a fascinating train wreck to gawk at, if we had another genuine example of the problem we have (not had) with QM. No idea if that’s what it was really like in biology circles though.
latveriandiplomat #19:
I’m a software person, and I thought the analogy was pretty good. The analogy made me think: “Oh, that’s a nice way to explain this idea to someone who does programming stuff.”
That’s all an analogy is: a stand-in which serves as a simplification to aid understanding. It doesn’t have to be perfect, and all analogies break when you stretch them. There are way more problems with PZ’s object analogy than deep vs. shallow copies and the like: in particular, in most programming languages there’s only one copy of the code for an object, so making a copy of the object doesn’t copy the code at all. Hence, you can’t have genetic variation with the code=DNA analogy.
Here’s another analogy that might be more accessible: imagine DNA is a big recipe book, and epigenetic marks are margin notes written in pencil like “you can get by with 1/2 as much salt here.”
So if DNA is the “code”, would epigenetics be the “subroutines”, or the “commands” to “run” the “subroutines”?
WMDKitty @22: epigenetics is more like a collection of boolean variables. Some of the code sets or clears the booleans, and other bits of code branch on them.
PZ’s object-oriented metaphor attributes too much elegance to genetics, IMHO. DNA is more like spaghetti code, packed with gotos and an ancient accumulation of insufferable hacks and kludges. The only reason the code works at all is that when it stops working you get fired, and your repo gets deleted.
From the point of view of someone like my self – WOW, I’m sure that’s cool, especially if it means we can laugh even harder at homeopaths, reincarnationists, karmic loaders et al.
But I will content myself with the layman’s understanding. The way DNA is “decoded” is affected by the environment both intra- and extra-cellular; sometimes the stuff that does that gets passed along temporarily like airline tags on luggage. I know it’s not right but it’s close enough for a 60+ year old non-academic like myself.
Any metaphor that likens DNA to computer code is flatout wrong.
And that XKCD describes evolution as an optimization process. Oy vey. Only goes to show programmers and math dudes think they know biology better than the biologists.
moarscienceplz@18
I have not been able to find the paper by the author in the movie describing the childhood diabetes with the grandfather living in a time of famine. The papers that I did find involves increased longevity with the grandfather living in a time of famine. This is what the video posted by williamgeorge@1 states at the end. Both my post and the video are talking about the same place and studied by the same author, as far as I can tell, so I do not know why there is a contradiction.
As we learn more about epigenetics the theory of evolution may need to be updated. Currently we define microevolution by the change in allele (gene) frequency in a population. But with epigenetics the alleles stay the same but how those genes are expressed change. Often people will describe gene expression as either being on or off like a light switch, but its better to think of it as a valve that you can turn on and adjust the flow. Epigenetics is just one valve of the pipeline from genes to proteins
applehead@25: “And that XKCD describes evolution as an optimization process. Oy vey.”
Isn’t it (in effect: obviously not “on purpose”) a local optimization process? Sort of like annealing (simulated or, I suppose, real) with rather random heating and quenching—likelier than not to get you into a local optimum, very unlikely to find a global optimum (even if such a thing exists).
I’m an almost completely non-programming math d00d. So I beg for kindness in your probable corrections of my misconceptions.
This is one where I have to regularly check for motivated reasoning and I guess I’m not totally sure how good a job I am doing. Epigenetics has huge explanatory power, but like many have said there needs to be larger, more carefully designed studies or just studies in general for many things. I agree with Igneous Rick @ #13, this can easily become the biological equivalent of “quantum”. We have lots of things from family temperament and personality over generations, to transgenerationally inherited trauma that can benefit from more understanding. But a typical use of this sort of science is as a political tool against others. For my part if people end up inheriting epigenetic predispositions to things like anxiety that just gets me pissed of at how society deals with things now. I can’t ignore how my family may be scarring the families of others.
I have Tourette’s Syndrome, ADHD and probable social OCD (needs diagnosed but patterns are there). There are literature references to imprinting from both parents in TS (stress/maternal stress seems to be a focus), ADHD has observations that include smoking grandmothers increasing likelihood of it’s appearance, and I have no problems with the idea that my social sensitivities are a result of predispositions and maintence by society after I was born. There are some very interesting potential relating to personality characteristics of TS/ADHD/social OCD and my heritage that involves a lot of physical and social conflict (long line of fundamentalist religious types and military). I think this is where personality and inheritance will start to be outlined because attempts to map genes find hundreds of them suggesting a system, and I can identify places where these conditions provide me with advantages.
Add to that things like the inheritance of introversion/extroversion and that odd correlation between parents who are engineers/scientists and autism and I think the near future will be very interesting. I just hope that it’s not “interesting”/
Well, I don’t have much problem with certain “specific” survival dependent factors being transferable. This makes sense as an adaptation, but it would be subtle and specific to very low level processes. Which is to say, maybe a smell could transfer, if it was “already” something strongly tied to survival, but not **everything in the known universe**, like so many of these people want it to be.
Hmm. I would say.. its more like the meta-data found in a configuration file. It might be, in some cases, something as simple as a switch, in other cases, it could be like a color setting (i.e., some level of variability), but it would be a color setting in “precisely” the sense that exist in configuration files, more or less – changing the color of one single thing in the end result, not “everything”, or, in the case of epigenes, just to reaction to one specific scent, which is strongly tied to things that a species has already run into in the past, and acquired the ability to tweak this way, for some reason. So.. no, not quite any of those things, though, a configuration file, in the world of code “might” define, “Use this process, instead of the other, or do this as well.”, for example, in some programs. So, is that a command, or just a setting?
With certain events like methylation I think only one DNA stand typically gets methylated so only one daughter cell will have the epigenetic advantage. I’m not sure about the other methods of epigenetics, but perhaps we’re even overstating how prevalent epigenetics based on this fact alone.
You might be overstating things here. When it comes to interactions like communities and all the different inputs and outputs which would result in cancer maybe we’re still probably far away from really understanding, but we have a good idea of things in single celled contexts, like the Lac operon and flagella etc.
@30 Marc
Prior to cell division DNA is replicated and humans (and other species) have what is called a maintenance DNA methylase that ensures that both daughter cells inherit the methylation pattern of the parent cell.